For many years, research on hallucinogenic agents has emphasized the hypothesis of possible interactions between the drugs and brain monoamines. However, definitive experiments in support of the hypothesis are sparse, mainly because few animal models seem to reflect accurately and predictably the state of monoamine chemistry in vivo. In this proposal, the influence of hallucinogens on endogenous serotonin will be studied two ways. By stimulating raphe nuclei electrically and recording in the hippocampus, we will establish a model in rat for serotonin function in a specific brain region. The model will be utilized to study the effects of hallucinogenic drugs (LSD, DMT, 5-Me-ODMT, mescaline, amphetamine) on the electrical signs of function. Secondly, we expect to correlate electrophysiological effects of psychotomimetics with their effects on rat behavior (the serotonin syndrome). Assays for brain norepinephrine, dopamine and serotonin will be employed with both models to determine if any hallucinogens act by altering monoamine concentrations. With these models, we will test the hypothesis that amphetamine and mescaline, as well as indolealkylamines, depend upon endogenous serotonin for their actions. Medical and social problems created by habitual abuse with these compounds provide evidence of our collective failure to cope with their widespread nonmedical use. With better information on molecular mechanisms of action, it should be possible to design treatment strategies for hallucinogen overdose and toxic reactions.